A Phase 2 interventional study of Alemtuzumab and Fludarabine in Sickle Cell Disease, sponsored by Emory University. Active, not recruiting at 15 sites in 2 countries. Open to participants aged 2 Years to 13 Years. Per ClinicalTrials.gov, last updated 2026-09-24.
Sponsored by Emory University · Phase 2, Interventional, and Treatment
This study aims to enroll 58 pre-adolescent (\<13 years) pediatric participants with sickle cell disease (SCD) who have a pre-adolescent sibling bone marrow donor. All participants will go through a pre-transplant evaluation to find out if there are health problems that will keep them from being able to receive the transplant. It usually takes 2 to 3 months to complete the pre-transplant evaluation and make the arrangements for the transplant. Once they are found to be eligible for transplant, participants will be admitted to the hospital and will start transplant conditioning. Conditioning is the chemotherapy and other medicines given to prepare them to receive donor cells. It prevents the immune system from rejecting donor cells. Conditioning will start 21 days before transplant. Once they complete conditioning, participants will receive the bone marrow transplant. After the transplant, participants will stay in the hospital for 4-6 weeks. After they leave the hospital, participants will be followed closely in the clinic. Outpatient treatment and frequent clinic visits usually last 6 to 12 months. Routine medical care includes at least a yearly examination for many years after transplant by doctors and nurses familiar with sickle cell disease and transplant. The researchers will collect and study information about participants for 2 years after transplant.
The use of HLA matched sibling donor (MSD) hematopoietic stem cell transplantation (HSCT) for sickle cell disease (SCD) is evolving. Because of the low risk for graft versus host disease (GVHD) associated with younger age, HSCT is increasingly being performed prior to adolescence. The use of less gonadotoxic reduced intensity regimens (RIC) are more commonly be utilized to lessen the risk for infertility. Finally, with the recognition that most children, even those who have asymptomatic to relatively mild courses, will develop debilitating morbidities as adults and ultimately suffer an early death, HSCT is being offered to children across a wider spectrum of SCD severity. Long reserved for severely affected children, HSCT is being performed for a growing number of less severely affected children, as well as children without disease manifestation.
This trial is designed to prospectively assess HSCT under these conditions. Eligibility will be limited to children less than 13 years of age who have an HLA MSD. SCD severity criteria will be broadened to include less severely affected children as well as those who are severely affected. A RIC regimen - fludarabine, alemtuzumab and melphalan (FAM) - will be employed. For GVHD prophylaxis, all patients will receive a calcineurin inhibitor and short course methotrexate.
This study has the following two specific aims:
Specific Aim #1: To prospectively assess the safety and efficacy of HSCT using FAM conditioning in children with SCD of varying severity who are under 13 years of age.
Specific Aim #2: To address current gaps in our understanding of the long-term effects of HSCT in children with SCD, by longitudinally assessing sickle cell related cerebrovascular disease, sickle cell related nephropathy and health related quality of life.
1,103 studies on the registry are indexed under Anemia, Sickle Cell; 235 are open to participants now.
This study's enrollment of 43 is close to the median of 40 across 750 interventional studies indexed under Anemia, Sickle Cell.
Browse Anemia, Sickle Cell studies →Emory University is the lead sponsor of 1,386 studies on the registry; 236 are open to participants now.
Of its 229 completed or terminated interventional studies of FDA-regulated products, 174 (76%) have results posted.
Counted across the registry records on this site, refreshed daily.
Patients must meet criteria for symptomatic SCD as defined below.
Severe disease:
Less severe disease: to qualify as having less severe disease, patients must not meet criteria for severe disease and must have one of the following:
Exclusion Criteria:
Active viral, bacterial, fungal or protozoal infection.
Children with SCD will received reduced intensity conditioning with fludarabine, alemtuzumab and melphalan (FAM) during HSCT with a HLA matched sibling donor. For GVHD prophylaxis, all patients will receive a calcineurin inhibitor (cyclosporine or tacrolimus) and short course methotrexate.
Drug: Alemtuzumab · Drug: Fludarabine · Drug: Melphalan · Drug: Cyclosporine · Drug: Tacrolimus · Drug: Methotrexate
Alemtuzumab will be administered by either subcutaneous (SQ) injection or IV. A test dose of alemtuzumab, 3 mg, is administered on the first day. If the test dose is tolerated, administration of three treatment doses will begin within 24 hours. The three treatment doses will be administered on consecutive days. On the first day, 10 mg/m2 will be given, 15 mg/m\^2 the second and 20 mg/m\^2 the third. Alemtuzumab will be started between Days -22 and -20, but all doses (test dose and three treatment doses) should be completed by Day -18.
Also known as: Campath
Fludarabine will be administered at 30 mg/m\^2 IV daily for five days (Days -7 to -3).
Also known as: Fludara, FLU
Melphalan will be administered at 140 mg/m\^2 IV on Day -3 following fludarabine administration.
Also known as: Alkeran, Evomela
For GVHD prophylaxis, calcineurin inhibitor (cyclosporine or tacrolimus) administration will commence no later than Day -2 (at least 36 hours before the stem cell infusion). Cyclosporine doses will be adjusted to maintain a level of 150-300 nanograms per milliliter (ng/ml) by mass spectrometry.
Also known as: Gengraf, Neoral, CsA
For GVHD prophylaxis, calcineurin inhibitor (cyclosporine or tacrolimus) administration will commence no later than Day -2 (at least 36 hours before the stem cell infusion). Tacrolimus doses will be adjusted to maintain a level of 8-15 ng/ml.
Also known as: Prograf, FK-506
For GVHD prophylaxis, methotrexate will be given intravenously at a dose of 15 milligrams per square meter (mg/m\^2) on day 1 and a dose of 10 mg/m\^2 on days 3, 6 and 11. Dosing shall be based on actual weight.
Also known as: MTX, Trexall, amethopterin
Immune Suppression-free, Rejection-free Survival
Immune suppression-free, rejection-free survival is defined as rejection-free survival off all systemic immunosuppressive agents. Participants who are off systemic immune suppression by 2-years post-transplant will be considered as being immune suppression free.
Time frame: Year 2
Regimen-Related Toxicity
Regimen-Related Toxicity (RRT) will be scored according to the Bearman scale. Major RRT, defined as grade 4 (causing death) in any organ system or grade 3 for pulmonary, cardiac, renal, oral mucosal, neurologic or hepatic, will be recorded. The assessment for RRT will be carried out on day 42 post-transplant.
Time frame: Day 42
Number of Neurological Complications
Neurological complications will be defined as any one of the following: seizures, intracranial hemorrhage, infarctive stroke (clinical or sub-clinical), and/or encephalopathy, including posterior reversible encephalopathy syndrome (PRES).
Time frame: Up to Year 2
Neutrophil Recovery
Neutrophil recovery is defined as the first of 3 consecutive days following the nadir that the absolute neutrophil count is at least 500/µl.
Time frame: Up to Year 2
Platelet Recovery
Platelet recovery is defined as the first day that the platelet count is at least 50,000/µl without a transfusion in the preceding 7 days.
Time frame: Up to Year 2
Graft Rejection
This endpoint will be met when donor engraftment fails to occur as evidenced by lack of neutrophil recovery or donor chimerism (5% donor derived cells on chimerism testing; for sorted testing, at least 5% of both lineages must be donor derived). This endpoint will also be met when there is initial donor engraftment but donor chimerism is lost.
Time frame: Up to Year 2
Sustained Donor Engraftment
This endpoint will be met when the patient is off all immune suppression (or is still on immune suppression as treatment for GVHD) by one year, has normal marrow function, has no acute signs of SCD and has at least 5% donor derived cells on chimerism testing (for sorted testing at least 5% of both lineages must be donor derived). This endpoint will be assessed through 2 years.
Time frame: Year 2
Cytomegalovirus (CMV) Viremia
CMV Viremia will be defined as the occurrence of a positive polymerase chain reaction (PCR) test prior to day 180.
Time frame: Day 180
CMV Invasive Disease
CMV invasive disease will be defined in accordance with the Blood and Marrow Transplant Clinical Trials Network Manual of Procedures.
Time frame: Up to Year 2
Post-transplant Lymphoproliferative Disorder
Post-transplant lymphoproliferative disorder will be defined in accordance with the Blood and Marrow Transplant Clinical Trials Network Manual of Procedures.
Time frame: Up to Year 2
Other Infections
Other Infections will be defined in accordance with the Blood and Marrow Transplant Clinical Trials Network Manual of Procedures.
Time frame: Up to Year 2
Early Onset Acute GVHD
Early onset (before day 100) acute GVHD (including all grades, and stratified by grades) will be assessed according to the Blood and Marrow Transplant Clinical Trials Network Manual of Procedures using the NIH consensus criteria.
Time frame: Day 100
Late Onset Acute GVHD
Late onset (after day 100) acute GVHD will be assessed according to the Blood and Marrow Transplant Clinical Trials Network Manual of Procedures using the NIH consensus criteria.
Time frame: Up to Year 2
Chronic GVHD
Chronic GVHD will be assessed according to the Blood and Marrow Transplant Clinical Trials Network Manual of Procedures using the NIH consensus criteria.
Time frame: Up to Year 2
Rejection-free Survival
Rejection-free survival is defined as survival with sustained engraftment.
Time frame: Up to Year 2
Overall Survival
Overall survival is defined as survival with or without rejection.
Time frame: Up to Year 2
Plan to share: No
This study is active, not recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
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